Using high-tech imaging in mice, researchers have made movies of autoimmune T cells destroying insulin-producing beta cells in the pancreas, the precursor of type 1 diabetes (see movie).

Researchers noted that the T cells moved randomly throughout the pancreas, almost aimlessly, until they came upon beta cells where they then released toxic substances that took hours to kill a few beta cells.

They identified specific blood vessels where the T cells entered the pancreas, which could help in the development of therapies to stop the T cells from entering the pancreas in the first place, they reported online in the Journal of Clinical Investigation.

They noted surprise that it took tens of millions of T cells in mice to destroy massive amounts of beta cells, suggesting an explanation of the long preclinical stage in type 1 diabetes. (The movies are available here at the end of the paper.)

-- C.K.

VIP Treatment for HIV

Antibodies that neutralize most strains of HIV have recently been found, leading to the hope that a vaccine that elicits them might be effective. But in mice at least, another approach appears to work, according to researchers led by Nobel laureate David Baltimore, PhD, of the California Institute of Technology in Pasadena, Calif.

In Nature, Baltimore and colleagues report that transferring the genes for the antibodies into mice with a humanized immune system – a process dubbed vectored immunoprophylaxis, or VIP – completely protected the animals from loss of CD4-positive T cells when challenged with high doses of HIV. The effect was long-lasting and robust, the researchers said, suggesting that a similar approach might work in people.

-- M.S.

Platelets on Demand

It may be possible to generate platelets in the laboratory for patients with clotting defects, laboratory research suggests.

Scientists from two universities in Japan plan to report at the American Society of Hematology (ASH) meeting later this month that they developed pluripotent stem cells from adult human cells, and then successfully coaxed them into an immortalized line of megakaryocytes, the progenitors of platelets.

According to an abstract appearing online ahead of the meeting, the researchers found that two genes -- INK4A and ARF -- were critical to senescence and apoptosis of the progenitors, which had frustrated earlier attempts to generate platelets ex vivo. Knocking them down allowed the megakaryocytes to survive indefinitely.

Moreover, platelets generated from the megakaryocyte line appeared to function normally when infused into immunodeficient mice.

ASH Secretary Charles Abrams, MD, told reporters on a conference call that the research was important because, unlike other blood cells, platelets isolated from donor blood are good only for a few days and therefore can't be banked. "There's always a shortage of platelets," he said, which would be eliminated if platelets could be manufactured on demand from cell lines.

Experimentally induced sympathetic activation -- mimicking the effects of chronic stress -- was associated with development of bone metastases in two different mouse models of breast cancer. Tumor burden in soft tissues did not increase.

Treating the animals with the beta-blocker propranolol inhibited activation by a validated stress protocol in both models.

"These data support a model whereby sympathetic activation induced by severe depression or stress shortens breast cancer patient survival by priming the 'vicious cycle' of bone destruction, prior to the increase in bone tumor burden," Preston Campbell, of Vanderbilt University in Nashville, Tenn., and colleagues reported in a poster presentation at the International Conference on Cancer-Induced Bone Disease in Chicago.

"It also suggests that medications like denosumab ... and beta-blockers ... may be able to inhibit bone metastasis and increase patient survival if given at an early time point after detection of the primary cancer."

-- C.B.

Green Tea and HCV

A compound found in green tea -- epigallocatechin-3-gallate (EGCG) – may help prevent reinfection with hepatitis C virus (HCV) after orthotopic liver transplantation.

For patients who require a liver transplant because of HCV-related complications, reinfection of the new organ remains a concern, underscoring the need for strategies to overcome the problem.

EGCG and its derivatives, epigallocatechin, epicatechin gallate, and epicatechin, have been shown to have antiviral and anti-oncogenic properties. So Eike Steinmann, PhD, of TWINCORE, Center for Experimental and Clinical Infection Research in Hannover, Germany, and colleagues treated hepatoma cell lines and primary human hepatocytes with EGCG and exposed them to HCV.

As reported in Hepatology, the researchers found that the compound prevented the virus from entering the cells by blocking viral attachment and also inhibited cell-to-cell spread. EGCG did not have any effect on HCV RNA replication, assembly, or release of progeny virions.

"This novel inhibitor may provide a new approach to prevent HCV infection, especially in the setting of liver transplantation of chronically infected HCV patients," the authors concluded.

-- T.N.

Alzheimer's Smell Loss Reversed in Mice

The loss of sense of smell experienced by patients with Alzheimer's disease may result from deposition of amyloid beta in the olfactory bulb of the brain – a process that was reversible in mice.

Olfactory loss is an early finding in Alzheimer's disease, occurring long before behavioral and cognitive changes begin, explained neuroscientist Daniel Wesson from Case Western Reserve University. To examine the process, he and his colleagues studied mice that overexpress human amyloid precursor protein and found that in early life, there was hyperactivity in the area of the brain where smells are processed, but as amyloid beta accumulated, the olfactory bulb became hypoactive, and the animals were no longer able to respond to smells they previously had recognized, even while spending more time sniffing.

The researchers then administered a compound that can remove the amyloid beta to the mice, and their olfactory responses returned to normal.

"Future clinical studies examining whether similar methods to reduce [amyloid beta] can prevent olfactory loss entirely or even just reduce it will be important in understanding the mechanisms of sensory loss in [Alzheimer's disease], they wrote in the Journal of Neuroscience.

-- N.W.

Antioxidants Implicated in Skin Cancer Disparity

Men may be more susceptible to UV skin damage than women because of lower antioxidant levels. That was the implication of mouse model research into the reason for threefold higher rates of a common type of skin cancer in men, reported in the Journal of Investigative Dermatology.

With repeated UV light exposure or other chronic or repeated inflammatory assaults on the skin, these cells persist and become immunosuppressive, the researchers noted.

"They can render helpful immune cells such as T cells or natural killer cells unable to recognize and eliminate cancer cells in the skin," a researcher explained in a press release. "As a result, men may be more susceptible to oxidative stress in the skin, which may raise the risk of skin cancer in men compared to women."

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